A novel receive-only liquid nitrogen (LN2)-cooled RF coil for high-resolution in vivo imaging on a 3-Tesla whole-body scanner

The design and operation of a receive-only liquid nitrogen (LN2)-cooled coil and cryostat suitable for medical imaging on a 3-T whole-body magnetic resonance scanner is presented. The coil size, optimized for murine imaging, was determined by using electromagnetic (EM) simulations. This process is therefore easier and more cost effective than building a range of coils. A nonmagnetic cryostat suitable for small-animal imaging was developed having good vacuum and cryogenic temperature performance. The LN2-cooled probe had an active detuning circuit allowing the use with the scanner's built-in body coil. External tuning and matching was adopted to allow for changes to the coil due to temperature and loading. The performance of the probe was evaluated by comparison of signal-to-noise ratio (SNR) with the same radio-frequency RF) coil operating at room temperature (RT). The performance of the RF coil at RT was also benchmarked against a commercial surface coil with a similar dimension to ensure a fair SNR comparison. The cryogenic coil achieved a 1.6- to twofold SNR gain for several different medical imaging applications: For mouse-brain imaging, a 100-mu m resolution was achieved in an imaging time of 3.5 min with an SNR of 25-40, revealing fine anatomical details unseen at lower resolutions for the same time. For heavier loading conditions, such as imaging of the hind legs and liver, the SNR enhancement was slightly reduced to 1.6-fold. The observed SNR was in good agreement with the expected SNR gain correlated with the loaded-quality factor of RF coils from the EM simulations. With the aid of this end-user-friendly and economically attractive cryogenic RF coil, the enhanced SNR available can be used to improve resolution or reduce the duration of individual scans in a number of biomedical applications

Formation and dimerization of the phosphodiesterase active site of the Pseudomonas aeruginosa MorA, a bi-functional c-di-GMP regulator

Diguanylate cyclases (DGC) and phosphodiesterases (PDE) respectively synthesise and hydrolyse the secondary messenger cyclic dimeric GMP (c-di-GMP), and both activities are often found in a single protein. Intracellular c-di-GMP levels in turn regulate bacterial motility, virulence and biofilm formation. We report the first structure of a tandem DGC–PDE fragment, in which the catalytic domains are shown to be active. Two phosphodiesterase states are distinguished by active site formation. The structures, in the presence or absence of c-di-GMP, suggest that dimerisation and binding pocket formation are linked, with dimerisation being required for catalytic activity. An understanding of PDE activation is important, as biofilm dispersal via c-di-GMP hydrolysis has therapeutic effects on chronic infections

Clinical frailty adds to acute illness severity in predicting mortality in hospitalized older adults: An observational study.

AIM: Frail individuals may be at higher risk of death from a given acute illness severity (AIS), but this relationship has not been studied in an English National Health Service (NHS) acute hospital setting. METHODS: This was a retrospective observational study in a large university NHS hospital in England. We analyzed all first non-elective inpatient episodes of people aged ≥75years (all specialties) between October 2014 and October 2015. Pre-admission frailty was assessed with the Clinical Frailty Scale (CFS) of the Canadian Study on Health & Aging, and AIS in the Emergency Department was measured with a Modified Early Warning Score (ED-MEWS<4 was considered as low acuity, and ED-MEWS≥4 as high acuity). A survival analysis compared times to 30-day inpatient death between CFS categories (1-4: very fit to vulnerable, 5: mildly frail, 6: moderately frail, and 7-8: severely or very severely frail). RESULTS: There were 12,282 non-elective patient episodes (8202 first episodes, of which complete data was available for 5505). In a Cox proportional hazards model controlling for age, gender, Charlson Comorbidity Index, history of dementia, current cognitive concern, and discharging specialty (medical versus surgical), ED-MEWS≥4 (HR=2.87, 95% CI: 2.27-3.62, p<0.001), and CFS 7-8 (compared to CFS 1-4, HR=2.10, 95% CI: 1.52-2.92, p<0.001) were independent predictors of survival time. CONCLUSIONS: We found frailty and AIS independently associated with inpatient mortality after adjustment for confounders. Hospitals may find it informative to undertake large scale assessment of frailty (vulnerability), as well as AIS (stressor), in older patients admitted to hospital as emergencies.This is the final version of the article. It first appeared from Elsevier via https://doi.org/ 10.1016/j.ejim.2016.08.03

Salivary testosterone measurement in women with and without polycystic ovary syndrome

Clinical and/or biochemical hyperandrogenism is one of the diagnostic criteria for PCOS. An evaluation of the role of salivary testosterone (salT) and androstenedione (salA) for the diagnosis of PCOS was undertaken in a cross sectional study involving 65 women without PCOS and 110 women with PCOS fulfilling all 3 diagnostic Rotterdam criteria. Serum and salivary androgen measurements were determined by LC-MS/MS. salT and salA were significantly elevated in PCOS compared to controls (P&lt;001). No androgen marker was more predictive than another using ROC curves, but multiple logistic regression suggested salT was more predictive than free androgen index (FAI)(p&lt;0.01). The combination of salT or FAI identified 100% of PCOS women. PCOS women with both biochemical and clinical hyperandrogenism as opposed to clinical hyperandrogenism alone showed a metabolic phenotype (p&lt;0.05) and insulin resistance(p&lt;0.001). PCOS patients with an isolated elevated FAI showed increased insulin resistance compared to those with an isolated salT(P&lt;0.05). salT appeared to be at least as predictive as FAI for the diagnosis of the classical PCOS phenotype, and the combination of salT or FAI identified 100% of PCOS patients. This suggests that salT measurement by LC-MS/MS holds the promise of complementing existing laboratory tests as a means of assessing hyperandrogenemia

Androsterone glucuronide to dehydroepiandrosterone sulphate ratio is discriminatory for obese Caucasian women with polycystic ovary syndrome

BACKGROUND: Androsterone glucuronide (ADTG) concentrations have been suggested as a marker of the effects of androgens at the target tissue level. As the mechanism for hyperandrogenemia in obese and nonobese polycystic ovary syndrome (PCOS) may differ, this study compared the different androgen parameters in non-obese compared to obese women with PCOS, and in normal subjects. METHODS: Eleven non-obese and 14 obese women with PCOS were recruited and compared to 11 control women without PCOS. Total testosterone, dehydroepiandrosterone sulphate (DHEAS), ADTG, and androstenedione were analysed using gold standard tandem mass spectrometry, and the free androgen index (FAI) was calculated. RESULTS: Total testosterone, ADTG and androstendione levels did not differ between non-obese (body mass index (BMI) ≤25 kg/m2) and obese PCOS (BMI >25 kg/m2) but all were significantly higher than for controls (p &lt; 0.01). The ADTG to DHEAS ratio was significantly elevated 39 ± 6 (p &lt; 0.01) in obese PCOS in comparison to non-obese PCOS and controls (28 ± 5 and 29 ± 4, respectively). The free androgen index (FAI) and insulin resistance (HOMA-IR) were significantly higher in obese PCOS compared to non-obese PCOS and controls (p &lt; 0.01). DHEAS was significantly higher in the non-obese versus obese PCOS (p &lt; 0.01). All androgen parameters were significantly lower and sex hormone binding globulin (SHBG) significantly higher in normal subjects compared to those with obese and non-obese PCOS. CONCLUSIONS: The ADTG:DHEAS ratio was significantly elevated in obese PCOS compared to non-obese PCOS and controls suggesting that this may be a novel biomarker discriminatory for obese PCOS subjects, perhaps being driven by higher hepatic 5α reductase activity increasing ADTG formation in these women

Searching for an Anthropo(s)cene in the uplands of mid Wales

This essay presents the responses of four creative writers to the highly modified landscapes of the Cambrian Mountains in mid Wales. Through a tour of the historic mine site of Cwmystwyth and the dams of Cwm Elan, our aims were to engage with the concept of the Anthropocene in a landscape that could be emblematic of the proposed new geological interval. Through poems and prose inspired by these landscapes, the physical, social, cultural, and political processes shaping them are explored. The pieces have a strong sense of place, and touch on themes of pollution of the environment by heavy metals, geomorphological impacts of dams, and the human stories associated with those places. We demonstrate the great potential of such places and landscapes as sites where artistic creativity and science can engage and collaborate to find ways of communicating concepts such as the Anthropocene and the anthroposcenic

Salivary and serum androgens with anti-Müllerian hormone measurement for the diagnosis of polycystic ovary syndrome

To determine the predictive value of a raised androgen level with an elevated anti-Müllerian hormone (AMH) for the diagnosis or exclusion of polycystic ovary syndrome (PCOS), a prospective cross-sectional study of 170 women (105 with PCOS type A and 65 normal) was undertaken. AMH was combined with one of, total serum testosterone (T); calculated free androgen index; salivary testosterone (salT); serum androstenedione (A); salivary androstenedione (salA). The diagnostic sensitivity and specificity of AMH (>35 pmol/l) alone for PCOS were 55% and 79% respectively. The diagnostic sensitivity and specificity of AMH (>35 pmol/l) with either an elevated T or raised FAI level for PCOS showed 100% specificity and a 100% positive predictive value. Conversely, diagnostic exclusion of PCOS was shown by an AM

Allocating patients to geriatric medicine wards in a tertiary university hospital in England: A service evaluation of the Specialist Advice for the Frail Elderly (SAFE) team.

The number of older patients admitted to acute hospitals has increased; however, their needs are heterogeneous and there is no gold-standard method of triaging them towards practicing comprehensive geriatric assessment (CGA). In our hospital, the SAFE (Specialist Advice for the Frail Elderly) team provide an initial geriatric assessment of all emergency admissions of patients aged ≥75 years (with some assessments also occurring in those aged 65 to 74 years) and recommend as to whether CGA in a dedicated Department of Medicine for the Elderly (DME) ward may be required. SAFE assessments include routine screening for geriatric syndromes using validated tools. Our aim was to compare the characteristics (age, gender, acute illness severity on admission as per modified early warning score (MEWS), Charlson Comorbidity Index, Clinical Frailty Scale (CFS), presence of dementia and delirium) and outcomes (length of stay, delayed discharge, inpatient mortality, discharge to usual place of residence, and new institutionalization) of patients listed to a DME ward, to those not listed. We analyzed all SAFE team assessments of patients admitted nonelectively between February 2015 and November 2016. Of 6192 admissions, 16% were listed for a DME ward. Those were older, had higher MEWS and CFS score, were more often affected by cognitive impairment, had longer hospital stay, higher inpatient mortality, and more often required new institutionalization. Higher CFS and presence of dementia and delirium were the strongest predictors of DME ward recommendation. Routine measurement of markers of geriatric complexity may help maximize access to finite inpatient CGA resources

Intramuscular fat in ambulant young adults with bilateral spastic cerebral palsy

BACKGROUND: It is known that individuals with bilateral spastic cerebral palsy (BSCP) have small and weak muscles. However, no studies to date have investigated intramuscular fat infiltration in this group. The objective of this study is to determine whether adults with BSCP have greater adiposity in and around their skeletal muscles than their typically developing (TD) peers as this may have significant functional and cardio-metabolic implications for this patient group. METHODS: 10 young adults with BSCP (7 male, mean age 22.5 years, Gross Motor Function Classification System (GMFCS) levels I-III), and 10 TD young adults (6 male, mean age 22.8 years) took part in this study. 11 cm sections of the left leg of all subjects were imaged using multi-echo gradient echo chemical shift imaging (mDixon). Percentage intermuscular fat (IMAT), intramuscular fat (IntraMF) and a subcutaneous fat to muscle volume ratio (SF/M) were calculated. RESULTS: IntraMF was higher with BSCP for all muscles (p = 0.001-0.013) and was significantly different between GMFCS levels (p < 0.001), with GMFCS level III having the highest IntraMF content. IMAT was also higher with BSCP p < 0.001). No significant difference was observed in SF/M between groups. CONCLUSION: Young adults with BSCP have increased intermuscular and intramuscular fat compared to their TD peers. The relationship between these findings and potential cardio-metabolic and functional sequelae are yet to be investigated